Project #1: Bone Histomorphometry Before and After Menopause Osteoporosis is a disease characterized by pathologic fractures in elderly women. The most important cause behind this is loss of bone tissue. The most important bone loss event in the life of a women is menopause. This proposal is designed to discover the disturbance in bone cell physiology which accounts for menopausal bone loss. To do this, 75 healthy, premenopausal women over age 47 have been recruited to undergo transilial bone biopsy after in vivo fluorochrome labeling. They are being biopsied again after labeling at 12 months after onset of menopause defined as cessation of menses. Serial bone density measurements are done throughout 9 total years of observation by the end of which all subjects will have undergone natural menopause. Serial measurements of calciotropic hormones and biochemical markers of bone remodeling are also being made. This study is unique because it is the first which examines bone cell function in vivo in healthy women just before and then during a time when the rate of bone loss is at its greatest, in the context of spontaneous, natural menopause. It should lead to a better understanding of the cellular mechanisms causing the bone loss associated with the most profound, predictable and universal bone-losing event in the lives of women. Knowledge of these mechanisms will permit better evaluation of possible interventions to prevent bone loss associated with menopause and the results could be extended to other bone losing events occurring in humans.